In recent years, medical technologies have been actively studied in the field of regenerative medicine, whereby a stem cell is transplanted to repair and regenerate target tissue and organ. Thus far, stem cells differentiating into mature cells of various tissues and organs have been discovered, clinical application in cell transplantation has been investigated.
For instance, c-kit-negative/CD31-positive/CD34-negative/Sca-1-positive mouse stem cell (refer to Oh H., et. Al., “Cardiac progenitor cells from adult myocardium: Homing, differentiation, and fusion after infarction”, Proc Natl Acad Sci USA, Vol. 100, 12313-12318, Oct. 14, 2003) and c-kit-positive/CD31-positive/CD34-positive rat stem cell (refer to Messina E., et. Al., “Isolation and expansion of adult cardiac stem cells from human and murine heart”, Circ Res., Vol. 95, 911-921, 2004 and Beltrami A P., et. Al., “Adult cardiac stem cells are multipotent and support myocardial regeneration”, Cell, Vol. 114, 763-776, Sep. 19, 2003) have been reported as cardiac tissue-derived myocardial stem cells. However, no studies have been carried out in human with the former myocardial stem cell, leaving clinical applicability unclear. Also, with the latter myocardial stem cell, proliferative ability is poor in addition to the isolation being extremely difficult, and there is the disadvantage that it is not suitable for large-scale culture for transplantation purposes. In addition, both above-mentioned myocardial stem cells are not pluripotent stem cells, and applications thereof are only to cell transplantation in heart.
In addition, in regard to myocardial stem cells, search for stem cells differentiating into cardiac myocyte is under way around bone marrow-derived hematopoietic cells and mesenchymal stem cells, in addition to cardiac tissue-derived myocardial stem cells; however, cells reported in prior art are not clinically applicable as the degree of differentiation into cardiac myocyte is extremely low.
As stated above, although cells that may function as stem cells have been found, the current situation is that almost none that are actually clinically applicable are known. With such prior art as the background, development is desired, of a pluripotent stem cell capable of differentiating into various mature cells such as cardiac myocyte, and applicable to regenerative therapeutic method.
Note that, so far, c-kit-negative/c-met-negative/CD34-negative/Sca-1-negative/Pax (3/7)-negative cardiac myocyte progenitor cells of muscle origin have been reported to be capable of differentiating into spontaneously beating cardiac myocyte (refer to WO2003/035838). However, the stem cell described in this WO2003/035838 can be isolated taking the muscle as the origin, and is known to be non-isolable from cardiac tissue (refer to Example 11 in WO2003/035838).